Displacement of [3H]-estradiol from human ERRalpha LBD expressed in Escherichia coli at 1 uM to 1 pM relative to estradiol

A series of 17alpha-(heteroaryl)vinyl estradiols was prepared to evaluate the influence of heteroatom on the affinity and efficacy of estrogenic ligands for the estrogen receptor-alpha ligand binding domain (ERalpha-LBD). The products demonstrated reduced binding affinity compared to the parent 17alpha-E-phenyl vinyl estradiol, but the binding was relatively independent of the heteroatom. The more ..

Abstract: A series of 17alpha-(heteroaryl)vinyl estradiols was prepared to evaluate the influence of heteroatom on the affinity and efficacy of estrogenic ligands for the estrogen receptor-alpha ligand binding domain (ERalpha-LBD). The products demonstrated reduced binding affinity compared to the parent 17alpha-E-phenyl vinyl estradiol, but the binding was relatively independent of the heteroatom. The greatest influence of the heteroatom was evident in the efficacy of the compounds as the thienyl derivatives 2f,g were more potent than either the pyridyl 2b-d or pyrimidinyl 2e analogs. The results suggest that a subtle interplay of interactions between the ligands and the receptor influences the biological response. (PMID: 22178552)